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Chemistry. 2018 Feb 6;24(8):1905-1912. doi: 10.1002/chem.201704493. Epub 2018 Jan 5.

Rationally Designed Chemically Modified Glycodendrimer Inhibits Streptococcus suis Adhesin SadP at Picomolar Concentrations.

Author information

1
Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520, Turku, Finland.
2
Centre for Analysis and Synthesis, Department of Chemistry, Lund University, POB 124, 221 00, Lund, Sweden.
3
Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, 3508 TB, Utrecht, The Netherlands.
4
Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Tykistökatu 6, 20520, Turku, Finland.
5
Department of Biosciences, Division of Biochemistry and Biotechnology, University of Helsinki, P.O.B. 56, 00014, Helsinki, Finland.

Abstract

Host cell surface carbohydrate receptors of bacterial adhesins are attractive targets in anti-adhesion therapy. The affinity of carbohydrate ligands with adhesins is usually found in the low μm range, which poses a problem for the design of effective inhibitors useful in therapy. In an attempt to increase the inhibitory power of carbohydrate ligands, we have combined the approach of chemical modification of ligands with their presentation as multivalent dendrimers in the design of an inhibitor of streptococcal adhesin SadP binding to its galactosyl-α1-4-galactose (galabiose) receptor. By using a phenylurea-modified galabiose-containing trisaccharide in a tetravalent dendrimeric scaffold, inhibition of adhesin at a low picomolar level was achieved. This study has resulted in one of the most potent inhibitors observed for bacterial adhesins and demonstrates a promising approach to develop anti-adhesives with the potential of practical applicability.

KEYWORDS:

AlphaScreen; Streptococcus suis; bacterial adhesion; carbohydrate receptors; dendrimers; glycolipids

PMID:
29094420
DOI:
10.1002/chem.201704493
[Indexed for MEDLINE]

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